DESCRIPTION: This revised renewal proposal addresses the problem of the highly variable expression of neurofibromatosis type 1 (NF1), a hereditary disease predisposing to neoplasia. The investigator proposes the hypothesis that a molecular explanation for this variability is that one of two RNA processing events may modulate NF1 expression. They are RNA editing and the expression of alternative NF1 transcripts. In Aim 1 Dr. Skuse proposes to assess the level of RNA editing in the tumors and unaffected tissues of NF-1 patients as well as controls, to identify the editing site as well as factors involved in the editing process, and inhibit editing to determine the effect on the cellular phenotype. In Aim 2, he states he will study the effect of NF1 RNA editing on RNA processing. The third aim will address the expression of alternative transcripts; two alternative transcripts will be manipulated to determine their effects on induced cellular differentiation. The final aim seeks to identify cellular factors involved with NF1 RNA editing and alternative NF1 transcript expression.